ABSTRACT BirthdefectsaretheleadingcauseofinfantmortalityintheUS.Birthdefectsalsohaveenormousassociated emotionalandfiscalcosts.TheCaliforniaCenter?sresearchefforts,bothindependentlyandincollaboration withotherCentersforBirthDefectsResearchandPreventioncontributingtotheNationalBirthDefects PreventionStudy(NBDPS)andtheBirthDefectsStudytoEvaluatePregnancyExposuresI(BD-STEPSI) havebeenattheforefrontofpublichealthbirthdefectsresearch.Withthisnewfundingopportunity(BD- STEPSII),ourCenterwillfurtherenhancescientificunderstandingofthepotentialcausesofspecificbirth defects,whichwillundoubtedlyhaveimportantimplicationsforriskassessmentandpreventionofcommon, costly,anddeadlybirthdefects.Inthisapplicationweproposethefollowingaims: Aim1:EnhancetheepidemiologicpublichealthresearchcapacityoftheCentersforBirthDefectsand ResearchandPreventionbyactivelyparticipatinginBD-STEPSIIinaregionoftheUSthatishighlydiversein itsrace/ethnicityaswellitsenvironmentalexposures. Aim2:UtilizedatafromBD-STEPSIandIIaswellasNBDPS(andlikelyotherdatasourcesuniqueto California)toconductrigorouscollaborativeandlocalstudiesthatwillidentifypotentialmodifiableriskfactors forselectedbirthdefects(andwhereappropriate,incombinationwithgeneticsusceptibility)toreducethe publichealthburdenofbirthdefectsintheUS. TheCaliforniaCenteriswell-equippedtocontributetoBD-STEPSII?itisaworldleaderinbirthdefects epidemiologyandhighlyexperiencedinthedevelopment,datacollectionanddisseminationofinformationfrom population-basedstudiesofbirthdefects,exemplifiedbyitsoutstandingperformancewithintheCDCCenters forBirthDefectsResearchanditshighlyinnovativeresearchportfolio.Theapplicationdescribeshowthe CaliforniaCenterwillaccomplishAims1and2andwilltherebyfurthertheknowledgebaseaboutcausesand preventionforhumanbirthdefects.TheCaliforniaCenterhasextensiveexperienceconductingresearch relatedtotheBD-STEPSIIareasoffocus,whichincludematernalchronicdiseasesandtheirtreatment, infectiousdiseaseinpregnancy,andmedications.Wehaveproposedseveralanalyticinquiries, complementedbytheuseofadditionalinnovativedatasetsandanalyticapproaches,whichwillenableusto collaborativelycontinueelucidatingthecontributionoftheseandothermodifiableriskfactorstobirthdefects.